Interstitial renal disease

2018 ◽  
Author(s):  
William G. Herrington ◽  
Aron Chakera ◽  
Christopher A. O’Callaghan
Keyword(s):  
Renal Disease ◽  
Interstitial Nephritis ◽  
Tubulointerstitial Nephritis ◽  
Interstitial Fibrosis ◽  
Acute Interstitial Nephritis ◽  
Renal Diseases ◽  
Interstitial Tissue ◽  
Renal Tubules ◽  
Early Disease ◽  
Tubular Atrophy

Tubulointerstitial renal diseases affect the renal tubules and/or the supporting interstitial tissue around them. The glomeruli are typically spared in early disease. Acute interstitial nephritis is characterized by an inflammatory infiltrate (often containing eosinophils). Chronic tubulointerstitial nephritis (TIN) is characterized by extensive tubular atrophy and interstitial fibrosis. The processes are clinically distinct but a prolonged acute interstitial nephritis will develop into chronic disease. This chapter looks at the etiology of interstitial renal disease, as well as its symptoms and clinical features, demographics, complications, diagnosis, and treatment.

Obstructive nephropathy and renal fibrosis

2002 ◽  
Vol 283 (5) ◽  
pp. F861-F875 ◽  
Author(s):  
Saulo Klahr ◽  
Jeremiah Morrissey
Keyword(s):  
Renal Disease ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Rodent Model ◽  
Renal Diseases ◽  
Obstructive Nephropathy ◽  
Therapeutic Approaches ◽  
Cellular Events ◽  
The Impact ◽  
Made In

Interstitial fibrosis has a major role in the progression of renal diseases. Several animal models are available for the study of renal fibrosis. The models of aminonucleoside-induced nephrotic syndrome, cyclosporin nephrotoxicity, and passive Heyman nephritis are characterized by molecular and cellular events similar to those that occur in obstructive nephropathy. Additionally, inhibition of angiotensin-converting enzyme exerts salutary effects on the progression of renal fibrosis in obstructive nephropathy. Unilateral ureteral obstruction (UUO) has emerged as an important model for the study of the mechanisms of renal fibrosis and also for the evaluation of the impact of potential therapeutic approaches to ameliorate renal disease. Many quantifiable pathophysiological events occur over the span of 1 wk of UUO, making this an attractive model for study. This paper reviews some of the ongoing studies that utilized a rodent model of UUO. Some of the findings of the animal model have been compared with observations made in patients with obstructive nephropathy. Most of the evidence suggests that the rodent model of UUO is reflective of human renal disease processes.

scholarly journals Nonneoplastic Renal Cortical Scarring at Tumor Nephrectomy Predicts Decline in Kidney Function

2013 ◽  
Vol 137 (4) ◽  
pp. 531-540 ◽  
Author(s):  
Steven P. Salvatore ◽  
Eugene K. Cha ◽  
James S. Rosoff ◽  
Surya V. Seshan
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Interstitial Fibrosis ◽  
Prognostic Significance ◽  
Preoperative Assessment ◽  
Tubular Atrophy ◽  
Hypertensive Nephropathy ◽  
Tumor Nephrectomy ◽  
End Stage

Context.—Evaluating nontumor portions of tumor nephrectomies is useful to diagnose nonneoplastic renal disease. Objective.—To determine the medical renal disease frequency and to assess the prognostic significance of the various renal pathologic variables with long-term follow-up in tumor nephrectomy patients. Design.—We reviewed nonneoplastic kidney sections of 456 consecutive cases from 1998 to 2008. Seventy-five cases were excluded (19 tumor compression, 25 no nonneoplastic tissue, 22 embolized kidneys, 9 end stage). Special staining, immunofluorescence, and/or electron microscopy was performed where appropriate. Vascular sclerosis was scored from mild to severe; interstitial fibrosis/tubular atrophy and global glomerulosclerosis (GS) were expressed as percentages. Follow-up, minimum 12 months, was evaluated in 156 cases. All renal pathologic variables were compared with regard to change in creatinine level from preoperative assessment to follow-up. Results.—Of 381 cases, 57 had additional medical renal disease (15%), most frequently diabetic nephropathy (28) and hypertensive nephropathy (11). Postoperative creatinine levels increased significantly in patients with severe arteriosclerosis or arteriolosclerosis, >5% GS, and >10% interstitial fibrosis/tubular atrophy. Seventy-four percent of cases with additional nonneoplastic diagnoses showed severe arteriolosclerosis. Higher corresponding GS was seen in the more affected vascular cases: mean, 5.56% GS for mild versus 23% GS for severe. Three patients progressed to renal failure 1 to 4 years after nephrectomy, 2 with hypertensive nephrosclerosis and 1 with diabetic nephropathy. Conclusions.—Medical renal disease was identified in 15% of tumor nephrectomy specimens. The degrees of vascular sclerosis, GS, and interstitial fibrosis/tubular atrophy are predictive of elevated creatinine levels in postnephrectomy patients. Prognostic implications of the nontumor pathology are important in nephrectomized patients.

scholarly journals A case of tubulointerstitial nephritis and uveitis syndrome after suspected drug-induced acute interstitial nephritis

2021 ◽  
Author(s):  
Yukiko Kitamura ◽  
shohei kuraoka ◽  
Koji Nagano ◽  
hiroshi tamura
Keyword(s):  
Interstitial Nephritis ◽  
Tubulointerstitial Nephritis ◽  
Late Onset ◽  
Acute Interstitial Nephritis ◽  
Suspected Drug ◽  
Drug Induced ◽  
Ophthalmic Examination ◽  
Tinu Syndrome ◽  
Eye Symptoms

Distinguishing between late-onset TINU syndrome and drug-induced AIN remains difficult given that patients with TINU syndrome may develop uveitis long after the onset of AIN. Therefore, ophthalmic examination is required not only upon diagnosis but also continuously or when eye symptoms, and relapse of urinary findings are observed.

Tubular and interstitial disease

2021 ◽  
pp. 140-184
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Disease Process ◽  
Analgesic Nephropathy ◽  
Tubular Epithelium ◽  
Tubular Atrophy ◽  
Important Group ◽  
The World ◽  
Interstitial Disease

Tubulointerstitial diseases refer to a group of disorders in which inflammatory cell infiltrates within the kidney interstitium and/or tubular epithelium are seen on kidney biopsy. These disorders constitute an important group of kidney diseases with varying prevalences and presentations due to a number of causes. It is difficult to estimate the worldwide incidence of tubular and interstitial disease as it is a histological diagnosis and biopsy rates vary substantially around the world. Increasing incidence of tubulointerstitial nephritis has been related to polypharmacy, particularly in the older population. Tubulointerstitial nephritis may present acutely as an immunologically mediated hypersensitivity reaction to an inciting agent—typically a drug or infection—or chronically as a part of a disease process leading to chronic interstitial fibrosis and tubular atrophy. Allergic interstitial nephritis, analgesic nephropathy, nephrotoxic metals, hyperuricemia, Balkan nephropathy, Mesoamerican nephropathy, aristolochic acid nephropathy, and other rare causes of tubulointerstitial nephritis are covered in this section. Isolated defects of tubular function, tubular disorder-related nephropathies, and electrolyte derangements also constitute important aspects of tubulointerstitial diseases.

Cytokines and L-arginine in renal injury and repair

1994 ◽  
Vol 267 (2) ◽  
pp. F197-F207 ◽  
Author(s):  
M. Ketteler ◽  
W. A. Border ◽  
N. A. Noble
Keyword(s):  
Growth Factor ◽  
Renal Disease ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Tgf Beta ◽  
Arginine Metabolism

Advances in molecular biology have identified cytokines as mediators of pathophysiological changes in chronic renal disease. Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of glomerular and interstitial fibrosis, whereas platelet-derived growth factor (PDGF) is involved in proliferative changes in chronic progressive renal diseases. Tumor necrosis factor-alpha and interleukins are expressed in experimental models of renal disease and are causes of inflammation and cell migration. Cytokines act by many different mechanisms, and one target of their action may be L-arginine metabolism. Since the discovery of the effector molecule nitric oxide (NO), generated from L-arginine, knowledge of this pathway has increased dramatically. It became evident that the L-arginine/NO pathway is of major importance in the regulation of hemodynamics and neurotransmission, in host defense against intracellular microorganisms, and in immunologic tissue injury. This pathway is induced by proinflammatory cytokines and possibly regulated by TGF-beta and PDGF. L-Arginine is also metabolized to L-ornithine, which can be processed to polyamines or to L-proline. As polyamines are important mediators of cell growth and L-proline is a substrate for collagen synthesis, both pathways, once activated, may be important in repair processes. It is likely that cytokines and L-arginine metabolism are interconnected and that both are involved in the inflammation, tissue repair, and fibrogenesis processes in the kidney. Dietary protein restriction in progressive renal diseases may substantially affect both systems. This review summarizes current knowledge about interactions of cytokines and L-arginine metabolism and the relevance to renal diseases.

scholarly journals Renal SGLT mRNA expression in human health and disease: a study in two cohorts

2019 ◽  
Vol 317 (5) ◽  
pp. F1224-F1230
Author(s):  
Vikas Srinivasan Sridhar ◽  
Jaya Prakash N. Ambinathan ◽  
Matthias Kretzler ◽  
Laura L. Pyle ◽  
Petter Bjornstad ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Mrna Expression ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Renal Tubules ◽  
Renal Protection ◽  
Health And Disease ◽  
Disease Study

Pharmacological Na+-glucose linked cotransporter (SGLT)2 inhibition is being examined as a renal protection strategy in nondiabetic chronic kidney disease. We quantified renal SGLT mRNA expression in healthy controls (HC), glomerulonephritis (GN), and diabetic kidney disease (DKD) to identify differences in expression across a spectrum of renal diseases. mRNA expression of SGLT1 and SGLT2 in renal tubules and glomeruli, obtained using microdissection and microarray techniques, was evaluated in two large cohorts. The European Renal cDNA bank included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network cohort included 124 adults with membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and IgA nephropathy. Within the European Renal cDNA bank, SGLT2 tubular and glomerular log2 mRNA expression significantly differed across HC, GN, and DKD ( P = 0.0009 and P = 0.0004), with the highest expression in HC. Within the Nephrotic Syndrome Study Network, there were no differences in SGLT log2 mRNA expression across GN subtypes. Tubular SGLT2 log2 mRNA expression positively correlated with estimated glomerular filtration rate (by the Modification of Diet in Renal Disease Study equation) and glycated hemoglobin ( r = 0.33 and 0.34, P < 0.05) and inversely correlated with interstitial fibrosis ( r = −0.21, P < 0.05). In conclusion, SGLT2 mRNA expression was lower in DKD compared with HC or GN and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity require further elucidation.

scholarly journals Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study

2022 ◽  
Vol 9 (1) ◽  
pp. e000576
Author(s):  
Shudan Wang ◽  
Ming Wu ◽  
Luis Chiriboga ◽  
Briana Zeck ◽  
Beatrice Goilav ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Membrane Attack Complex ◽  
Staining Intensity ◽  
Cross Sectional Study ◽  
Renal Tubules ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
Complement C9

IntroductionTreatment failures for lupus nephritis (LN) are high with 10%–30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.MethodsIn this cross-sectional study, LN kidney biopsies were assessed for MAC deposition by staining for Complement C9, a component of the MAC. Chromogenic immunohistochemistry was performed on paraffin-embedded human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197). Tubular C9 staining intensity was analysed as present versus absent. IFTA was defined as minimal (<10%), mild (10%–24%), moderate (25%–50%) and severe (>50%).ResultsRenal biopsies from 30 patients with LN were studied. There were 24 (80%) female sex, mean age (SD) was 33 (12) years old and 23 (77%) had pure/mixed proliferative LN. Tubular C9 staining was present in 7 (23%) biopsies. 27 patients had minimal-to-mild IFTA and 3 patients had moderate IFTA. Among the C9 + patients, 3 (43%) had moderate IFTA as compared with none in the C9- group, p=0.009. C9 + patients had higher median (IQR) proteinuria as compared with C9- patients: 6.2 g (3.3–13.1) vs 2.4 g (1.3–4.6), p=0.001 at the time of biopsy. There was no difference in estimated glomerular filtration rate (eGFR) between the C9 + and C9- groups.ConclusionThis study demonstrated that tubular MAC deposition is associated with higher degree of IFTA and proteinuria, which are predictors of progression to ESRD. These results suggest that tubular MAC deposition may be useful in classification of LN. Understanding the role of complement in tubulointerstitial injury will also identify new avenues for LN treatment.

Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease

2021 ◽  
pp. ASN.2021010044
Author(s):  
Ghazal Quinn ◽  
Amin Abedini ◽  
Hongbo Liu ◽  
Ziyuan Ma ◽  
Andrew Cucchiara ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Kidney Function ◽  
Structural Damage ◽  
Interstitial Fibrosis ◽  
Early Disease ◽  
Tubular Atrophy ◽  
Histologic Analysis ◽  
Complementary Method ◽  
Disease Stages

Background: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as estimated glomerular filtration rate (eGFR) and proteinuria, is unclear. Methods: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. Results: At chronic kidney disease (CKD) stages 3-5, eGFR estimated reasonably well the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of such damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis, IFTA, or both at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation even at early disease stages. Conclusions: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

Drug-induced chronic tubulointerstitial nephritis

2015 ◽  
Author(s):  
Hassan Izzedine ◽  
Victor Gueutin
Keyword(s):  
Renal Disease ◽  
Drug Exposure ◽  
Tubulointerstitial Nephritis ◽  
Chemotherapeutic Agents ◽  
Analgesic Nephropathy ◽  
Small Subset ◽  
Low Grade ◽  
Tubular Dysfunction ◽  
Drug Induced ◽  
Tubular Atrophy

The chronic form of drug-induced tubulointerstitial nephritis (CTIN) is an insidious disease and most probably represents the common final response pattern of the kidney to a variety of agents (including analgesics, lithium, antineoplastic chemotherapeutic agents, like cisplatin and nitrosoureas, and immunosuppressive drugs, such as ciclosporin and tacrolimus). Drug-induced CTIN is usually asymptomatic, presenting with slowly progressive renal impairment. Because of its insidious nature, CTIN is often diagnosed incidentally on routine laboratory screening or evaluation of CKD. The diagnosis of drug-induced CTIN largely depends on the history of exposure to a nephrotoxic drug. Clinical investigations may show modest elevation in serum creatinine, evidence of tubular dysfunction (e.g. renal tubular acidosis), or Fanconi syndrome (i.e. aminoaciduria, glycosuria, hypophosphataemia, and hypouricaemia). Urinalysis may be normal or show low-grade proteinuria (< 1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. Analgesic nephropathy is possibly still the most common category of CTIN worldwide. The amount of phenacetin-acetaminophen combination required to cause CTIN has been estimated to be at least 2–3 kg over many years. Lithium-induced CTIN occurs in a small subset of patients receiving long-term lithium therapy, who have had repeated episodes of lithium toxicity, with high serum drug levels. CTIN induced by ciclosporin or tacrolimus is common among patients receiving kidney, heart, liver, and pancreas transplants. The mechanism appears to be dependent largely on the potent vasoconstrictive effects of these drugs. The recognition of a potential association between a patient’s renal disease and exposure to a drug is crucial, because, unlike many other forms of renal disease, drug-induced CTIN can be prevented and even reversed, by avoiding additional drug exposure.

scholarly journals ACUTE INTERSTITIAL NEPHRITIS

1898 ◽  
Vol 3 (4-5) ◽  
pp. 393-420 ◽  
Author(s):  
W. T. Councilman
Keyword(s):  
Infectious Diseases ◽  
Blood Vessels ◽  
Interstitial Nephritis ◽  
Scarlet Fever ◽  
Plasma Cells ◽  
Acute Interstitial Nephritis ◽  
Lymphoid Cells ◽  
Interstitial Tissue ◽  
Microscopical Examination ◽  
Boundary Zone

Acute interstitial nephritis is found in the infectious diseases of children, particularly in diphtheria and scarlet fever, but may be met with in other infectious diseases. The disease is characterized by general and focal infiltration of the interstitial tissue of the kidney with cells which correspond to those which Unna has described under the name of plasma cells. The focal character of the infiltration is marked; even in the cases in which all parts of the kidney show some interstitial cellular infiltration the cells are most abundant in certain foci. These foci are found in three places: in the boundary zone of the pyramids, in the sub-capsular region of the cortex, and around the glomeruli. A considerable number of cases is found in which the blood-vessels of the boundary zone of the pyramids contain nnmbers of lymphoid and plasma cells without any infiltration of the interstitial tissue. The new cells in the interstitial tissue are due to emigration from the blood-vessels and multiplication by mitotic division of the cells which have emigrated. The cells can emigrate as plasma. cells or as lymphoid cells, and the latter may change into plasma cells in the tissues. In the normal individual, plasma cells may be formed in the mucous membrane of the intestine, where they practically form the entire tissue between the epithelium and the muscularis mucosa, and to a limited extent in the spleen. In diphtheria, in scarlet fever, and probably in a number of infectious diseases, plasma cells are formed in great numbers in the spleen and bone-marrow, and to some extent in the lymphatic glands. In the spleen they are formed from the cells of the Malpighian bodies, which are often principally composed of them, and to some extent from the cells in the pulp. They are formed from the lymphoid cells. No adequate explanation is found for the focal character of the lesions in the kidneys. There is some ground for believing that the physical conditions of the circulation may have something to do with their accumulation in the vessels in certain places. It is also possible that in the interstitial foci there may be soluble substances which exert a positive chemotaxis for them. Such substances may be foundin the urine, which may exert its influence on the interstitial tissue in different places. The explanation of the foci cannot be found in primary focal degeneration of the epithelium. Epithclial degeneration in these cases is always present, but it is diffuse. In foci where it is more intense and due to the interstitial changes, polynuclear leucocytes are found in the tissue, in the degenerated epithellum and in the tubules. Folynuclear lencocytes and not plasma cells are attracted by degenerated tissue. The foci are not due in these cases to the local action of bacteria. In a number of the cases in which interstitial nephritis was found the kidneys were shown to be sterile both by cultures and by microscopical examination. In cases where bacteria were present they were found only in small numbers in cultures and not on microscopical examination, and their connection with the foci could not be demonstrated. In three cases plasma cells were found in the interstitial tissue in definite bacterial diseases of the kidney. In these cases they were not found in connection with the lesions produced directly by the bacteria, but in the periphery of the purulent foci.

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